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The physician’s psychoactive medication resource guide
25% of your patients taking an antidepressant will have
weight gain and the weight gain is directly caused by the antidepressant.
Brand name (Asendin)
Amoxapine (Asendin) Asendin. Asendin side effects, warnings, precautions, adverse effects,
overdose, withdrawal symptoms and Asendin natural alternatives. Before you begin the spiral down
with these drugs, try giving your body what it really wants.
Amoxapine is a tricyclic antidepressant of the dibenzoxazepine class. The mechanism of clinical
action of amoxapine in man is not well understood. Amoxapine is not a monoamine oxidase (MAO)
inhibitor. In animals, amoxapine inhibits the re-uptake of norepinephrine and, to a lesser degree, of
serotonin, at adrenergic nerve endings and blocks the response of dopamine receptors to dopamine.
Its major metabolite, 8-hydroxyamoxapine, has similar norepinephrine uptake inhibiting activity but
greater serotonin blocking effect than the parent compound, while the other major metabolite, 7-
hydroxyamoxapine, has a dopamine receptor blocking effect.
Amoxapine is absorbed rapidly and reaches peak blood levels approximately 90 minutes after
ingestion. It has a serum elimination half-life of 8 hours and is almost completely metabolized in the
liver to 7-hydroxyamoxapine and 8-hydroxyamoxapine. The major active metabolite, 8-
hydroxyamoxapine, has a serum half-life of 30 hours, while 7-hydroxyamoxapine is present in serum
only in low concentrations with a half-life of 6.5 hours. Most of the drug is excreted in the urine and
smaller amounts in the feces. The urinary metabolites appear in conjugated form as glucuronides
with 33% of the dose accounted for as the 8-hydroxy metabolite and 25% as the 7-hydroxy
metabolite. Only 2% is excreted unchanged. In vitro tests show that amoxapine binding to human
serum protein is approximately 90%. The drug crosses the placental barrier and is excreted in
human milk. The initial clinical effect usually occurs within 2 weeks of administration, but may be
seen in some patients within 4 to 7 days.
The relief of symptoms of depression. Patients who have failed to respond satisfactorily to other
antidepressants may show response to amoxapine.
Hypersensitivity to dibenzoxazepine compounds. It should not be given concomitantly with MAO
inhibitors. When replacing MAO inhibitors with amoxapine, a minimum of 14 days should be allowed
to elapse after the former is discontinued. Amoxapine should then be initiated cautiously with gradual
increase in dosage until optimum response is achieved. Amoxapine is also contraindicated during
the acute recovery phase following myocardial infarction and in the presence of acute congestive
Tardive dyskinesia is known to occur in patients treated with neuroleptics with antipsychotic
properties and other drugs with substantial neuroleptic activity. It has also been observed with
amoxapine administration (see Adverse Effects). Although the dyskinetic syndrome may remit
partially or completely if the medication is withdrawn, it is irreversible in some patients. At the present
time there is uncertainty as to whether neuroleptic drugs differ in their potential to cause tardive
Since there is a significant prevalence of this syndrome associated with the use of neuroleptic drugs,
and since there is no known effective treatment, chronic use of these drugs should generally be
restricted to patients for whom neuroleptics are known to be effective and for whom there is no alternative therapy available with better
risk acceptability. If manifestations of tardive dyskinesia are detected during the use of amoxapine, the drug should be discontinued.
The risk of a patient developing tardive dyskinesia and of the syndrome becoming irreversible appear to increase with the duration of
treatment and the total amount of drugs administered, although, in some instances, tardive dyskinesia may develop after relatively
short periods of treatment at low doses. The risk of developing tardive dyskinesia may, therefore, be minimized by reducing the dose of
the neuroleptic drug used and its duration of administration, consistent with the effective management of the patient's condition.
Continued use of neuroleptics should be periodically reassessed.
Withdrawal Emergent Neurological Signs:
As with antipsychotic agents, withdrawal emergent dyskinetic signs have been reported in some patients on maintenance therapy with
amoxapine following its discontinuation. The signs are very similar to those described under Tardive Dyskinesia (see Adverse Effects),
except that they are usually less persistent. Although it is not known whether gradual withdrawal will decrease the incidence of
withdrawal emergent neurological signs, gradual withdrawal would appear to be advisable.
Since tricyclic agents are known to reduce the seizure threshold and since grand mal seizures have occurred at therapeutic dosage
levels (<1%), extreme caution should be taken in administering the drug to patients with a history of convulsive disorders. Concurrent
administration of ECT and amoxapine may be hazardous and, therefore, such treatment should be limited to patients for whom it is
Because of its anticholinergic properties, amoxapine should be used with extreme caution in patients with a history of urinary retention,
angle closure glaucoma or increased intraocular pressure.
Tricyclic antidepressant drugs, particularly when given in high doses, can induce sinus tachycardia, changes in conduction time and
arrhythmias. A few instances of unexpected death have been reported in patients with cardiovascular disorders. Myocardial infarction
and stroke have also been reported with drugs of this class. Therefore, amoxapine should be administered with extreme caution to
patients with a history of cardiovascular disease, those with circulatory lability and elderly patients. In such cases, treatment should be
initiated with low doses with progressive increases only if required and tolerated, and the patients should be under close surveillance at
all dosage levels.
Close supervision is required when amoxapine is given to hyperthyroid patients or those receiving thyroid medication because of the
possibility of cardiovascular toxicity. Tricyclic drugs may also block the antihypertensive effects of guanethidine and related
Pregnancy and Lactation:
Safety during pregnancy and lactation has not been established. It should not be used in women of childbearing potential or nursing
mothers, unless, in the opinion of the physician, the potential benefits to the patient outweigh the possible hazards to the fetus.
Amoxapine is excreted in breast milk.
Amoxapine is not recommended for use in children since safety and efficacy in this age group have not been established.
Since amoxapine has a sedative component to its action, patients should be advised against driving or engaging in activities requiring
mental alertness and physical coordination until their response to the drug has been well established.
Patients should be warned that the effects of other drugs acting on the CNS, such as alcohol, barbiturates and other CNS depressants,
may be potentiated by amoxapine.
The possibility of suicide in seriously depressed patients may remain until significant remission occurs. Such patients should be closely
supervised throughout therapy and consideration should be given to the possible need for hospitalization. This type of patient should
not have easy access to large quantities of amoxapine.
Tricyclic antidepressants may precipitate or aggravate psychotic manifestations in schizophrenic patients and hypomanic or manic
episodes in manic-depressive patients. This may require a reduction of dosage, discontinuation of the drug, and/or administration of an
Tricyclic antidepressants may also give rise to paralytic ileus, particularly in the elderly and in hospitalized patients. Therefore,
appropriate measures should be taken if constipation occurs.
When amoxapine is given concomitantly with anticholinergic or sympathomimetic drugs, close supervision and careful adjustment of
dosages are required.
Amoxapine should be discontinued prior to elective surgery for as long as the clinical situation will allow.
Amoxapine should be used with caution in patients with impaired liver function or with a history of hepatic damage or blood dyscrasias.
Periodic blood counts and liver function tests should be performed when patients receive amoxapine in large doses or over prolonged
As with other dopamine antagonists, amoxapine elevates serum prolactin levels. Tissue culture experiments indicate that
approximately one-third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if the prescription of
amoxapine is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea,
amenorrhea, gynecomastia and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown
for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of neuroleptic drugs.
Neither clinical studies, nor epidemiologic studies conducted to date, however, have shown an association between chronic
administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this
Caution should be exercised if amoxapine is administered together with cimetidine since cimetidine inhibits tricyclic antidepressant
metabolism, and clinically significant increases in plasma levels of amoxapine may occur.
Although some of the adverse reactions included in the following list have not been reported with amoxapine, pharmacological
similarities among the tricyclic antidepressants require that each of the reactions be considered when prescribing amoxapine. With
amoxapine, as with other tricyclic antidepressant drugs, the side effects most often reported are sedation and anticholinergic effects.
Drowsiness, fatigue, excitement, agitation, restlessness, insomnia, nightmares, hypomania, anxiety, confusion, disorientation,
disturbed concentration, delusions, hallucinations, activation of latent psychosis.
Seizures, alteration in EEG patterns, dizziness, tremors, extrapyramidal symptoms, numbness, tingling, paresthesias of the
extremities, peripheral neuropathy, tinnitus, syndrome of inappropriate ADH (antidiuretic hormone) secretion.
Extrapyramidal symptoms reported with amoxapine include: akinesia, akathisia, chorea, cogwheel rigidity, dysarthria, mask-like facies,
oculogyric crisis, torticollis and dyskinesia, including tardive dyskinesia. Although most of these symptoms have been reported
infrequently, the possibility of their occurrence should be borne in mind when prescribing amoxapine.
As with antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy with amoxapine or may appear
after drug therapy has been discontinued (withdrawal tardive dyskinesia). The risk appears to be greater in elderly patients on high-
dose therapy, especially females. The symptoms are persistent and in some patients may be irreversible. The syndrome is usually
characterized by rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g. protrusion of tongue, puffing of cheeks,
puckering of mouth, chewing movements), but may also be manifested by abnormal involuntary movements of extremities and other
extrapyramidal symptoms, such as akathisia.
There is, at present, no known effective treatment for tardive dyskinesia; anticholinergic agents may worsen the symptoms of this
syndrome and the results from studies with other agents (e.g. dopamine agonists, cholinergics, GABA agonists) are not clear.
Therefore, it is suggested that amoxapine be discontinued if symptoms of tardive dyskinesia appear, and the patient be switched to a
On no account should the dosage be increased in an attempt to mask the syndrome. It has been reported that fine vermicular
movements of the tongue may be an early sign of the syndrome, and, if the medication is stopped at that time, the syndrome may not
Hypotension, hypertension, tachycardia, palpitations, syncope, atrial arrhythmias (including premature atrial contractions and
fibrillation), heart block, stroke and cardiac arrest have been reported with amoxapine. A quinidine-like effect and other reversible ECG
changes such as flattening or inversion of T waves, bundle branch block, depressed ST segments, prolonged conduction time and
asystole have been reported with other tricyclic antidepressants.
Dry mouth, blurred vision, disturbances of accom- modation, mydriasis, constipation, nasal stuffiness, delayed micturition, sublingual
adenitis, paralytic ileus, urinary retention, dilation of the urinary tract, precipitation of latent and aggravation of existing glaucoma,
Increased or decreased libido, impotence, menstrual irregularity, testicular swelling, painful ejaculation, inhibition of orgasm, breast
enlargement and galactorrhea in the female, gynecomastia in the male, elevation and lowering of blood sugar levels, and increased
Allergic or toxic:
Pruritus, skin rash, photosensitization, edema, drug fever, leukopenia, urticaria, petechiae, obstructive jaundice, bone marrow
depression, including agranulocytosis, eosinophilia, purpura and thrombocytopenia, toxic epidermal necrolysis and neuroleptic
Nausea, epigastric distress, vomiting, flatulence, abdominal pain, diarrhea, peculiar taste, stomatitis.
Weakness, headache, weight gain or loss, excessive appetite, anorexia, increased perspiration, urinary frequency, lacrimation,
alopecia, parotid swelling, black tongue, hepatitis.
Abrupt cessation of treatment with tricyclic antidepressants after prolonged administration may produce nausea, headache and
malaise. These symptoms are not indicative of addiction. Withdrawal emergent dyskinesia has been reported with amoxapine.